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1.
The genetic heterogeneity of hereditary transthyretin amyloidosis in a sample of the Brazilian population 下载免费PDF全文
Carolina Lavigne‐Moreira Vanessa D. Marques Marcus V. M. Gonçalves Mauricio F. de Oliveira Pedro J. Tomaselli José C. Nunez Osvaldo J. M. do Nascimento Amilton A. Barreira Wilson Marques Jr 《Journal of the peripheral nervous system : JPNS》2018,23(2):134-137
2.
Isabel Conceição Alejandra González‐Duarte Laura Obici Hartmut H.‐J. Schmidt Damien Simoneau Moh‐Lim Ong Leslie Amass 《Journal of the peripheral nervous system : JPNS》2016,21(1):5-9
Transthyretin familial amyloid polyneuropathy (TTR‐FAP) is a rare, progressive, life‐threatening, hereditary disorder caused by mutations in the transthyretin gene and characterized by extracellular deposition of transthyretin‐derived amyloid fibrils in peripheral and autonomic nerves, heart, and other organs. TTR‐FAP is frequently diagnosed late because the disease is difficult to recognize due to phenotypic heterogeneity. Based on published literature and expert opinion, symptom clusters suggesting TTR‐FAP are reviewed, and practical guidance to facilitate earlier diagnosis is provided. TTR‐FAP should be suspected if progressive peripheral sensory‐motor neuropathy is observed in combination with one or more of the following: family history of a neuropathy, autonomic dysfunction, cardiac hypertrophy, gastrointestinal problems, inexplicable weight loss, carpal tunnel syndrome, renal impairment, or ocular involvement. If TTR‐FAP is suspected, transthyretin genotyping, confirmation of amyloid in tissue biopsy, large‐ and small‐fiber assessment by nerve conduction studies and autonomic system evaluations, and cardiac testing should be performed. 相似文献
3.
Familial amyloidotic polyneuropathy is an autosomal dominant neurodegenerative disorder caused by accumulation of mutated transthyretin (TTR) amyloid fibrils in different organs and prevalently around peripheral nerves. We have constructed transgenic flies, expressing the clinical amyloidogenic variant TTRL55P and the engineered variant TTR-A (TTRV14N/V16E) as well as the wild-type protein, all in secreted form. Within a few weeks, both mutants but not the wild-type TTR demonstrated a time-dependent aggregation of misfolded molecules. This was associated with neurodegeneration, change in wing posture, attenuation of locomotor activity including compromised flying ability and shortened life span. In contrast, expression of wild-type TTR had no discernible effect on either longevity or behavior. These results suggest that Drosophila can be used as a disease-model to study TTR amyloid formation, and to screen for pharmacological agents and modifying genes. 相似文献
4.
Gian Luca Vita Claudia Stancanelli Luca Gentile Costanza Barcellona Massimo Russo Gianluca Di Bella Giuseppe Vita Anna Mazzeo 《Neuromuscular disorders : NMD》2019,29(3):213-220
Hereditary transthyretin amyloidosis (hATTR) is a life-threatening multisystemic disease with sensory-motor peripheral neuropathy, cardiomyopathy and dysautonomia. Although the six-minute walk test (6MWT) is one of the most popular clinical tests to assess functional exercise capacity in cardiopulmonary and neuromuscular diseases, little is known about 6MWT in evaluating hATTR patients. A prospective single-center pilot study was performed in twenty hATTR patients, comparing 6MWT with widely used outcome measures. After 18 months, fourteen patients were re-evaluated. 6MWT performance was highly related with familial amyloidotic polyneuropathy stage and polyneuropathy disability score, and with CMT examination score, neuropathy impairment score-lower limbs and Kumamoto score. There was no correlation with compound autonomic dysfunction test, modified body mass index and numerous indices of heart dysfunction. After 18 months, familial amyloidotic polyneuropathy stage and polyneuropathy disability score systems were not able to reveal any significant change, whereas all other outcome measures significantly worsened. Among the outcome measures monitoring the neuropathic disturbances, neuropathy impairment score-lower limbs showed the highest responsiveness to change (adjusted effect size: 0.79), followed by CMT examination score (0.67), Kumamoto scale (0.65), 6MWT (0.62). 10MWT showed a very small value (0.21). Compound autonomic dysfunction test had a large value (0.91) whereas modified body mass index a small/moderate value (0.49). 6MWT is a simple and sensitive tool to monitor neuropathic involvement but not cardiac dysfunction in hATTR course. 相似文献
5.
Haruki Koike MD PhD Rina Hashimoto MD Minoru Tomita MD Yuichi Kawagashira MD PhD Masahiro Iijima MD PhD Tomohiko Nakamura MD PhD Hirohisa Watanabe MD PhD Hideya Kamei MD PhD Tetsuya Kiuchi MD PhD Gen Sobue MD PhD 《Muscle & nerve》2012,46(6):961-964
Introduction: Information related to the long‐term follow‐up of neuropathy in patients with familial amyloid polyneuropathy after liver transplantation is still scarce. Methods: We describe the neuropathic features of 3 patients with the transthyretin Val30Met mutation. Each patient underwent liver transplantation at an early stage of neuropathy, as indicated by the absence of motor dysfunction and relative preservation of myelinated fibers in sural nerve biopsy specimens. Results: Although the patient with late‐onset disease (at age 60 years) presented with the least amount of amyloid deposition, he had neuropathic progression after liver transplantation. An older early‐onset (at age 40 years) patient reported a slight exacerbation of both somatic and autonomic neuropathic symptoms 10 years after transplantation. However, the younger early‐onset (at age 28 years) patient did not exhibit characteristics suggestive of neuropathy 7 years after transplantation. Conclusion: Aging may determine the progression of neuropathy after liver transplantation. Muscle Nerve, 2012 相似文献
6.
Mahima Kapoor Martha Foiani Amanda Heslegrave Henrik Zetterberg Michael P. Lunn Andrea Malaspina Julian D. Gillmore Alexander M. Rossor Mary M. Reilly 《Journal of the peripheral nervous system : JPNS》2019,24(4):314-319
Hereditary transthyretin amyloidosis (ATTRm) causes a disabling peripheral neuropathy as part of a multisystem disorder. The recent development of highly effective gene silencing therapies has highlighted the need for effective biomarkers of disease activity to guide the decision of when to start and stop treatment. In this study, we measured plasma neurofilament light chain (pNfL) concentration in 73 patients with ATTR and found that pNfL was significantly raised in ATTRm patients with peripheral neuropathy compared to healthy controls. Furthermore, pNFL correlated with disease severity as defined by established clinical outcome measures in patients for whom this information was available. These findings suggest a potential role of pNfL in monitoring disease activity and progression in ATTRm patients. 相似文献
7.
J. Wixner P. Karling A. Rydh R. Hörnsten U. Wiklund I. Anan O. B. Suhr 《Neurogastroenterology and motility》2012,24(12):1111-e568
Background Gastrointestinal (GI) complications are common in hereditary transthyretin amyloidosis and an autonomic dysfunction has been considered to explain these symptoms. The aim of this study was to investigate the impact of autonomic neuropathy on gastric emptying in hereditary transthyretin amyloidosis and to relate these findings to nutritional status, GI symptoms, gender, and age at disease onset. Methods Gastric emptying was evaluated with gastric emptying scintigraphy. Spectral analysis of the heart rate variability and cardiovascular responses after tilt test were used to assess the autonomic function. The nutritional status was evaluated with the modified body mass index (s‐albumine × BMI). Key Results Gastric retention was found in about one‐third of the patients. A weak correlation was found between the scintigraphic gastric emptying rate and both the sympathetic (rs = ?0.397, P < 0.001) and parasympathetic function (rs = ?0.282, P = 0.002). The gastric emptying rate was slower in those with lower or both upper and lower GI symptoms compared with those without symptoms (median T50 123 vs 113 min, P = 0.042 and 192 vs 113 min, P = 0.003, respectively). Multiple logistic regression analysis showed that age of onset (OR 0.10, CI 0.02–0.52) and sympathetic dysfunction (OR 0.23, CI 0.10–0.51), but not gender (OR 0.76, CI 0.31–1.84) and parasympathetic dysfunction (OR 1.81, CI 0.72–4.56), contributed to gastric retention. Conclusions and Inferences Gastric retention is common in hereditary transthyretin amyloidosis early after onset. Autonomic neuropathy only weakly correlates with gastric retention and therefore additional factors must be involved. 相似文献
8.
Fernanda Wajnsztajn Yungher Arreum Kim Amelia Boehme Inna Kleyman Louis H Weimer Mathew S Maurer Thomas H Brannagan 《Journal of the peripheral nervous system : JPNS》2020,25(3):265-272
To propose a correlation between polyneuropathy and ATTRwt based on retrospective analysis of patients with ATTRwt. We reviewed 151 ATTRwt patients followed by the amyloid cardiac clinic (group A) for symptoms of neuropathy and 12 patients with ATTRwt evaluated in the Neurology Department (group B) with objective measures of neuropathy. Medical history, electrodiagnosis, laboratory and skin biopsies were assessed; 30.5% of group A had neuropathy symptoms. Alternative explanations for neuropathy symptoms were explored, including, age, gender, BMI, diabetes mellitus, B12 deficiency. No difference was observed for BMI, age, gender and spine disease for those with and without neuropathic symptoms (P > .05). All of group B (n = 12) were diagnosed with neuropathy, confirmed by electrodiagnostic testing or skin biopsy, while two patients had not yet developed cardiac symptoms. We observe a higher prevalence of neuropathic symptoms in ATTRwt patients than previously believed. Neuropathic symptoms may precede cardiac symptoms. Our findings suggest a possible causative relationship that requires further investigation. 相似文献
9.
Yazaki M Yamashita T Kincaid JC Scott JR Auger RG Dyck PJ Benson MD 《Muscle & nerve》2002,25(2):244-250
We report a 52-year-old woman with a novel transthyretin (TTR) variant serine replacing alanine at residue 25 [Ala25Ser (Serine 25)], who showed a unique clinical picture with a relatively acute onset neuropathy within a few days of an influenza vaccination, progressing to a severe degree within 2 years. Sural nerve biopsy revealed amyloid deposition in the endoneurium. Sequencing of the proband's DNA revealed a G to T transversion at the first position of codon 25 of TTR gene. DNA analysis of this family showed the same mutation in her older sister and a niece, but her parents did not have the mutation. Haplotype analysis revealed the mutation to be clearly linked to haplotype III allele inherited from the proband's father. These results indicate this novel Serine 25 mutation originated in the paternal germline mosaicism. It is possible that the vaccination had an influence on the unique clinical picture, but this remains uncertain. 相似文献
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Comparison between small bowel manometric patterns and full‐thickness biopsy histopathology in severe intestinal dysmotility 下载免费PDF全文
A. Accarino R. F. Cogliandro S. Landolfi A. Gori E. Boschetti J. R. Malagelada V. Stanghellini F. Azpiroz R. De Giorgio 《Neurogastroenterology and motility》2018,30(3)
12.
Simon Podnar Stayko Sarafov Ivailo Tournev Gregor Omejec Janez Zidar 《Clinical neurophysiology》2017,128(4):505-511
Objective
To systematically study peripheral nerve morphology in patients with transthyretin (TTR) amyloidosis and TTR gene mutation carriers using high-resolution ultrasonography (US).Methods
In this prospective cross-sectional study we took a structured history, performed neurological examination, and measured peripheral nerve cross-sectional areas (CSAs) bilaterally at 28 standard locations using US. Demographic and US findings were compared to controls.Results
Peripheral nerve CSAs were significantly larger in 33 patients with familial amyloid polyneuropathy (FAP) compared to 50 controls, most dramatically at the common entrapment sites (median nerve at the wrist, ulnar nerve at the elbow), and in the proximal nerve segments (median nerve in the upper arm, sciatic nerve in the thigh). Findings in 21 asymptomatic TTR gene mutation carriers were less marked compared to controls, with CSAs being larger only in the median nerve in the upper arm. Nerve CSAs correlated with abnormalities on nerve conduction studies.Conclusion
Using US, we confirmed previous pathohistological and imaging reports in FAP of the most pronounced peripheral nerve thickening in the proximal limb segments.Significance
Similar to US findings in diabetic and vasculitic neuropathies these predominantly proximal locations of nerve thickening may be attributed to ischaemic nerve damage caused by poor perfusion in the watershed zones along proximal limb segments. 相似文献13.
14.
Rainer J. Lüttmann MD Inga Teismann MD Ingo W. Husstedt MD PhD E. Bernd Ringelstein MD PhD Gregor Kuhlenbäumer MD PhD 《Muscle & nerve》2010,41(5):679-684
Hereditary amyloidosis of the Finnish type (HAF, or familial amyloid polyneuropathy type IV) is an autosomal dominant disease that has been described most commonly in the Finnish population but has also been found in some other countries. Herein we report the first German family whose members suffer from this condition. There are no known Finnish ancestors. We performed clinical and electrophysiological examinations in 22 members of this family. All symptomatic family members suffered from facial palsy, and most of them had peripheral neuropathy. One patient had confirmed corneal lattice dystrophy. Additional symptoms were hypoglossal nerve involvement in 5 patients and oculomotor nerve palsy in 1 patient. The lips of all older patients appeared thickened. The causative G654A mutation in the gelsolin gene was found in all affected family members. Muscle Nerve, 2010 相似文献
15.
Incidence of nonamyloidogenic mutations in the transthyretin gene in patients with autonomic and small fiber neuropathy 下载免费PDF全文
Introduction: Mutations of the transthyretin (TTR) gene have been associated with polyneuropathy; the protein product has a tendency to form amyloid deposits in the peripheral nervous system. Methods: Patients with small fiber neuropathy (SFN) with or without autonomic symptoms were given skin biopsies to assess nerve fiber density. Any patient with autonomic symptoms was assessed for autonomic neuropathy (AN). If testing revealed no clear cause of neuropathy, the TTR gene was sequenced. Results: Thirty‐six percent of patients were found to harbor at least 1 mutation in the TTR gene sequence (variants of unknown significance [VUS]). Of 24 patients diagnosed with SFN, 8% of patients had a point mutation (c76G>A). Of those patients who were diagnosed with both SFN and AN, 68% of patients had a VUS within the TTR gene (c76G>A, c337‐18G>C). Conclusions: The results suggest an association between presumed nonamyloidogenic mutations in the TTR gene and the development of AN and SFN. Muscle Nerve 57 : 140–142, 2017 相似文献
16.
Massimo Russo Anna Mazzeo Claudia Stancanelli Rita Di Leo Luca Gentile Gianluca Di Bella Fabio Minutoli Sergio Baldari Giuseppe Vita 《Journal of the peripheral nervous system : JPNS》2012,17(4):385-390
Transthyretin‐related familial amyloidotic polyneuropathy (TTR‐FAP) usually presents itself as a progressive sensorimotor polyneuropathy with severe autonomic dysfunction and cardiomyopathy. Eighteen patients carrying the Leu64 mutation underwent a series of regular follow‐ups, including: neurological examination, electroneurography, electromyography, electrocardiography and echocardiography, blood analysis, a questionnaire on autonomic symptoms, cardiovascular autonomic tests and a 99mTc‐DPD examination study. A late onset of a slowly progressive disease which reached its terminal stage after about 10 years was observed. The onset was mainly a length‐dependent sensory neuropathy, although a focal onset with carpal tunnel syndrome was detected in three patients. At the onset of the disease, autonomic dysfunction was present in a small number of patients, but, within a few years, this had manifested in all members of the sample group. The only extra‐neurological manifestations were cardiac related. It is reasonable to consider Southern Italy as an endemic focus of TTR‐FAP. An underestimation of disease prevalence could be caused by a late onset of FAP, which can manifest in patients up to their late 70s. Follow‐up of asymptomatic individuals may permit the early detection of symptoms and signs, allowing a detailed record of the natural history of the disease from the beginning and facilitating prompt treatment. 相似文献
17.
J. E. KELLOW P. M. LANGELUDDECKE G. M. ECKERSLEY M. P. JONES C. C. TENNANT 《Neurogastroenterology and motility》1992,4(1):47-52
Recordings of fasting duodenojejunal motor activity were obtained during a controlled 20-min period of psychological relaxation in 10 patients with irritable bowel syndrome (IBS) and 10 healthy subjects. The IBS group showed a significant decline in their level of arousal (on both cardiovascular and subjective measures) in response to relaxation; such alterations were minimal in the control group. Both groups, however, demonstrated significant inhibition of phase 2 activity (motility index, contractile frequency and amplitude) of the migrating motor complex in response to relaxation, and the magnitude of the response did not differ between the two groups. Clustered contractile activity present in 4 IBS patients was also suppressed during the relaxation period. There were no correlations between changes in the level of arousal and the degree of motor suppression in either IBS patients or controls. These findings demonstrate that psychological relaxation therapy can profoundly influence patterns of small bowel motility, and shed light on the mechanisms by which psychological intervention therapy appears to be effective in IBS. 相似文献
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F. Ahlfors H. Linander M. Lindström B. Veress H. Abrahamsson 《Neurogastroenterology and motility》2011,23(4):347-e159
Background Few families with autosomal dominant forms of chronic idiopathic pseudo‐obstruction (CIP) have been identified and reported. Methods We compared two families by clinical, laboratory, histopathologic, and genealogical investigations. Ten patients (pts) (five women) from two families, A and B, both with a family history suggesting autosomal dominant CIP, were investigated. Key Results All pts had chronic diarrhea, nine of ten pts had chronic abdominal pain and seven of ten chronic vomiting. Median age for onset of symptoms was 23 (A) and 34 years (B). None had dysphagia, urogenital, neurologic, or ocular symptoms. Small bowel transit and jejunal culture were abnormal in eight of nine. Manometry showed severe jejunal hypomotility in the fasting and fed state and absence of normal phase III in all nine pts and neuropathy‐like duodenal alterations in eight of nine. Progress to overt CIP had occurred in six pts. Histopathologic re‐evaluation (three pts) showed that criteria of visceral degenerative neuropathy were fulfilled in both families including intranuclear inclusions in all three pts. Genealogic exploration using the unique Swedish Register for Catechetical Meetings disclosed that the two families with all likelihood shared a male ancestor in the 1890s. Conclusions & Inferences The compiled results with striking similarities between family A and B together with genealogy findings indicate that this is one, large kindred with a familial autosomal dominant form of intestinal degenerative neuropathy often progressing to CIP but without extra‐intestinal manifestations. This is the fourth and, so far, the largest family reported with these characteristics. 相似文献